Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the publication of research conducted by Merck scientists on the discovery and development of verubecestat, an investigational small molecule inhibitor of the enzyme beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), for the potential treatment of Alzheimer's disease (AD). The research was published online in the latest edition of the peer-reviewed journal Science Translational Medicine and includes results from the Phase 1 clinical trials in healthy volunteers and people with AD . The efficacy and safety of verubecestat is currently being evaluated in two pivotal Phase 3 clinical trials, EPOCH and APECS, for the treatment of mild-to-moderate AD and prodromal AD, respectively. "The development of a potential disease modifying therapy for treatment of Alzheimer's disease has long been a focus of biomedical research," said Dr. Michael Egan, vice president, clinical development neurosciences, Merck Research Laboratories. "We believe this research has the potential to contribute important evidence regarding the amyloid hypothesis, a leading scientific theory for what causes Alzheimer's disease, and we look forward to seeing the data from our ongoing Phase 3 clinical trials." BACE1 is an important enzyme in the initiation of the toxic Aß peptide production in the brain. Researchers believe that sustained, selective inhibition of BACE1 leading to a significant decrease in the toxic Aß peptide production is a promising means for therapeutic intervention. This hypothesis has not yet been demonstrated in clinical studies. Historically the development of selective BACE1 inhibitors with properties allowing oral absorption and the ability to cross the blood-brain-barrier to the site of action in the brain proved technically challenging. Detailed analysis of the BACE1 protein structure and function by Merck scientists over many years was used to design a series of drug-like compounds with an ability to inhibit the protein, both in vitro and in the central nervous system (CNS) of preclinical animal models. This process yielded the lead compound verubecestat. Verubecestat produced significant CNS Aß lowering in rodents and non-human primates treated for 6- to 9-months. Verubecestat's preclinical safety and tolerability profile supported its progression into human clinical testing for chronic use.